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Withdrawal from chronic cocaine in rats: A model of depression
616
Abstracts
mOL PSYCHIATRY 1996:39:500-666
that a rapid mechanism Clr.ists in brain tissue to inacUvat", these lipids and terminate their biological actions.
398. NEUROPSYCHOLOGICAL DEFICITS IN MARIJUANA SMOKERS D.A. Yurgelun-Todd, S.A. Gruber, & H.G. Pope, Jr. Consolidated Department of Psychiatry, Harvard Medical School McLean Hospital. Belmonl, MA Previous studies have atlcmptcd to assess the residual effects of chronic marijuana usc on neuropsychological perform:mce, however. method· ologie limitations have often obscured clear results. We compared the neuropsychological data of 6S heavy users to 64 light users. while controlling for potential confounding variubles. such as estimated levels of premorbid cognitive functioning. :md usc of alcohol and olher substances in the two groups. Heavy users were delined as those who had smoked an average of27.8 ± 2.S days of the past 30 days. and displ3yed urinary cannabinoids. while light users smoked an average of 3.0 ± 2.2 days of the l:I5t30 days and displayed no urinary cannabinoids. A bailer)' of neuropsychological tests wa.~ administered to subjects after they completed a minimum of 19 hours of supervised nbstcmioll from marijuana. Findin~s suggest that heavy marijuana usc is associalctl wilh deficits in Ihe atlcntionallcxccutivc system, a.~ sussested by reduced verbal nucncy, increased pcrscYeralivc errors on the WeST, lind reduced learning. demonstrntcd by a reduction in lotal items recalled on Ihe CVLT. The :lbility to retain newly learned information remained relalively unimpaired in the heavy users, demonstrated by a lack of decay between immediate Dnd delayed conditions on the CVLT and lhe Roy Osterrieth Complex Figure. These results suggest thaI lllthough mari· juana may produce some residual impairment in memory function, the principal errect seems to be on the llllenlional/executive system. Given Ihe relatively short period of abstinence from marijullna used in this study. it remains unclenr whether impairment is due to n residue of the drug in tl\e brnin. or if it represents a more severe. toxic effect on brain tissue.
399. WITHDRAWI\L FROM CHRONIC COCAINE IN RATS: A MODEL OF DEPRESSION
M.H. Baumann & R.B. Rothman Clinical Pllychopharmacology Section, NIDAINIH. IRP. BaltimoTC. MD21224 Withdraw
cocaine exposure on responsivencss to S-RT drugs in mts. Male Sprngue.Dnwley rals filled wilh indwelling jugular cathelers received cocaine (IS mglkg, ip. bid) or saline for 7 consecutive days. Acute injections of the 5-HT rele:l5inj; agent fennununine (1.5 mglkg, iv). the 5·HT,a receptor agonist 8-0H-DPAT (SO I-Lsfks. iv). the 5·HT2..r.!c receptor agonist 001 (100. p.glkg. iv). or saline were given at 42 h after tile chronic dosing regimen. Repeated blood samples were removed after challenge injections and plasma was assayed for conicosterone (CORT) Ilnd prolactin (PRL) by RIA. All 5·HT drugs increased plasma CORT and PRL in chronic s3line- and cocaine-treated rats. However, in cocaine·treated rats the CORT response 10 fcnfluramine and the PRL response 10 g-OH-DPAT were significantly blunted whcre:ts the PRL responsc to DOl was potentiatcd. Our data agree with the findings of others and suggest multiple alterations in S·HT transmission during cocaine withdrawal. A survey of the c1inicill literature indic:lles that changes in 5·HT rcsponsj'ICtlCSS (ie attcnuulcd sensitivity to 5·HT· releasing Dgcnts and S·HT La receptor ngonists) arc similar in depressed human paticnl~ and cocainc-withdmwn rats, The evidence lIull cocaine withdrawal in rots may serve as a vi3ble model of major depression in humans wi \I be discussed.
400. INDIVIDUAL DIFFERENCES IN CORTICAL AND SUBCORTICAL GABAA BINDING AND BEHAVIOR RJ. Gruen l ,2, K. Wenberg J , M. Selim3 , AJ. Friedhoff2, & C.W. Bradberry3,4 Dcpts. of lpsychology and ~Psychiatry. New York University, New York. NY 10003; Depls. of ~Psychi:ltry nnd
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Abstracts
mOL PSYCHIATRY 1996:39:500-666
that a rapid mechanism Clr.ists in brain tissue to inacUvat", these lipids and terminate their biological actions.
398. NEUROPSYCHOLOGICAL DEFICITS IN MARIJUANA SMOKERS D.A. Yurgelun-Todd, S.A. Gruber, & H.G. Pope, Jr. Consolidated Department of Psychiatry, Harvard Medical School McLean Hospital. Belmonl, MA Previous studies have atlcmptcd to assess the residual effects of chronic marijuana usc on neuropsychological perform:mce, however. method· ologie limitations have often obscured clear results. We compared the neuropsychological data of 6S heavy users to 64 light users. while controlling for potential confounding variubles. such as estimated levels of premorbid cognitive functioning. :md usc of alcohol and olher substances in the two groups. Heavy users were delined as those who had smoked an average of27.8 ± 2.S days of the past 30 days. and displ3yed urinary cannabinoids. while light users smoked an average of 3.0 ± 2.2 days of the l:I5t30 days and displayed no urinary cannabinoids. A bailer)' of neuropsychological tests wa.~ administered to subjects after they completed a minimum of 19 hours of supervised nbstcmioll from marijuana. Findin~s suggest that heavy marijuana usc is associalctl wilh deficits in Ihe atlcntionallcxccutivc system, a.~ sussested by reduced verbal nucncy, increased pcrscYeralivc errors on the WeST, lind reduced learning. demonstrntcd by a reduction in lotal items recalled on Ihe CVLT. The :lbility to retain newly learned information remained relalively unimpaired in the heavy users, demonstrated by a lack of decay between immediate Dnd delayed conditions on the CVLT and lhe Roy Osterrieth Complex Figure. These results suggest thaI lllthough mari· juana may produce some residual impairment in memory function, the principal errect seems to be on the llllenlional/executive system. Given Ihe relatively short period of abstinence from marijullna used in this study. it remains unclenr whether impairment is due to n residue of the drug in tl\e brnin. or if it represents a more severe. toxic effect on brain tissue.
399. WITHDRAWI\L FROM CHRONIC COCAINE IN RATS: A MODEL OF DEPRESSION
M.H. Baumann & R.B. Rothman Clinical Pllychopharmacology Section, NIDAINIH. IRP. BaltimoTC. MD21224 Withdraw
cocaine exposure on responsivencss to S-RT drugs in mts. Male Sprngue.Dnwley rals filled wilh indwelling jugular cathelers received cocaine (IS mglkg, ip. bid) or saline for 7 consecutive days. Acute injections of the 5-HT rele:l5inj; agent fennununine (1.5 mglkg, iv). the 5·HT,a receptor agonist 8-0H-DPAT (SO I-Lsfks. iv). the 5·HT2..r.!c receptor agonist 001 (100. p.glkg. iv). or saline were given at 42 h after tile chronic dosing regimen. Repeated blood samples were removed after challenge injections and plasma was assayed for conicosterone (CORT) Ilnd prolactin (PRL) by RIA. All 5·HT drugs increased plasma CORT and PRL in chronic s3line- and cocaine-treated rats. However, in cocaine·treated rats the CORT response 10 fcnfluramine and the PRL response 10 g-OH-DPAT were significantly blunted whcre:ts the PRL responsc to DOl was potentiatcd. Our data agree with the findings of others and suggest multiple alterations in S·HT transmission during cocaine withdrawal. A survey of the c1inicill literature indic:lles that changes in 5·HT rcsponsj'ICtlCSS (ie attcnuulcd sensitivity to 5·HT· releasing Dgcnts and S·HT La receptor ngonists) arc similar in depressed human paticnl~ and cocainc-withdmwn rats, The evidence lIull cocaine withdrawal in rots may serve as a vi3ble model of major depression in humans wi \I be discussed.
400. INDIVIDUAL DIFFERENCES IN CORTICAL AND SUBCORTICAL GABAA BINDING AND BEHAVIOR RJ. Gruen l ,2, K. Wenberg J , M. Selim3 , AJ. Friedhoff2, & C.W. Bradberry3,4 Dcpts. of lpsychology and ~Psychiatry. New York University, New York. NY 10003; Depls. of ~Psychi:ltry nnd
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